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PMID: 8475083 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The role of "indirect" recognition in initiating rejection of skin grafts from major histocompatibility complex class II-deficient mice.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 90 ·No. 8 ·1993-04-15 ·Pages 3373-7

Auchincloss H, Lee R, Shea S, Markowitz JS, Grusby MJ, Glimcher LH

Abstract

In vitro studies have revealed several pathways by which T cells can respond to alloantigens, including CD4+ direct responses to allogeneic class II antigens, CD8+ direct responses to allogeneic class I antigens, and CD4+ "indirect" responses to peptides of alloantigens presented in association with responder class II molecules. In vivo studies of skin graft rejection, however, have so far provided clear evidence for the contribution of only the two direct pathways and not for indirect recognition. We have used major histocompatibility complex class II-deficient mice as donors to test the role of indirect recognition in rejection of skin grafts. Class II-deficient skin was always rejected without delay by normal recipients. Removal of recipient CD8+ cells (to leave the animals dependent on CD4+ function) or depletion of recipient CD4+ cells revealed that CD4+ cells were usually involved and sometimes absolutely required in this rapid rejection. Since the donor grafts lacked class II antigens, the CD4+ cells must have recognized donor antigens presented in association with recipient class II molecules. These results therefore indicate that indirect recognition can initiate rapid skin graft rejection.

MeSH Terms
Animals CD4 Antigens/immunology CD8 Antigens/immunology Genes, MHC Class II Graft Rejection/immunology Graft Survival/immunology Histocompatibility Antigens Class II/genetics Lymphocyte Depletion Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL Mice, Inbred Strains Mice, Mutant Strains Skin Transplantation/immunology T-Lymphocytes/immunology Time Factors
Chemicals
CD4 Antigens CD8 Antigens Histocompatibility Antigens Class II
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Auchincloss H
Department of Surgery, Massachusetts General Hospital, Boston 02114.
Lee R
Shea S
Markowitz J S
Grusby M J
Glimcher L H
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.90.8.3373
Published
1993-04-15
Pages
3373-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC46302
Subset
IM
Grants
NIAID NIH HHS · AI21569 · United States
NHLBI NIH HHS · HL18646 · United States
NHLBI NIH HHS · HL36372 · United States
External Links
PubMed source DOI: 10.1073/pnas.90.8.3373 PMC Full Text View journal details
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